安定对大鼠脊髓损伤的保护作用及GABA_A受体拮抗剂对此作用的影响

DIAZEPAM PROTECT SPINAL CORD FROM SECONDARY DEGENERATION AFTER SPINAL CORD INJURY AND THE INFLUENCE BY THE ANTAGONISTS OF GABA_A RECEPTOR

应用大鼠脊髓挤压伤模型来研究安定对大鼠挤压伤模型脊髓损伤后的保护作用,及GABAA受体拮抗剂bicuculline对此作用的影响。实验大鼠分为对照组、安定组、安定联合bicuculline组及bicuculline组,应用大鼠脊髓挤压伤模型观察药物作用72h后各组大鼠脊髓损伤体积变化。结果显示对照组大鼠脊髓损伤体积为(18.21±1.14)mm3;安定组大鼠脊髓损伤体积为(12.11±1.61)mm3,明显小于对照组(P<0.01);安定联合bicuculline组大鼠脊髓损伤体积为(16.34±1.59)mm3,大于安定组(P<0.01),但仍小于对照组(P<0.01);bicuculline组大鼠脊髓损伤体积为(18.45±1.98)mm3;与对照组相比无明显差异(P>0.05)。结论安定可明显减轻大鼠脊髓挤压损伤后的脊髓损伤程度,而GABAA受体拮抗剂bicuculline可拮抗此作用,说明安定通过与GABAA受体结合,可提高GABA与GABAA受体的结合力,从而上调GABA的抑制作用,减少谷氨酸的兴奋性毒性作用以达到保护脊髓的作用。

The function of diazepam protecting spinal cord from spinal cord injury(SCI) and the interreaction with bicuculline, a GABA_A receptor antagonist, were investigated in a compressive spinal cord injury model. The rats were randomly divided into control group; diazepam group; diazepam plus bicuculline group and bicuculline group, the total lesion volumes of each spinal cord 72 h after SCI were observed. Results show: the total lesion volume of control group is (18.21±1.14)mm3, in diazepam group is (12.11±1.61)mm3, the volume markedly decreased comparing to control group(P<0.01),in diazepam plus bicuculline group, the total leision volume is ^(16.34±1.59)mm3 , bigger than diazepam group(P<0.01)but smaller than control group(P<0.01), and in bicuculline group , the volume is (18.45±1.98)mm3, not significantly different from that of the control (P>0.05). The present study shows that diazepam can effectively attenuate the secondary injury following SCI, and bicuculline can block the protective effect of diazepam, indicated that diazepam, as a positive allosteric modulator, can bind to the GABA_A receptor, increase the appetency of GABA recognition sites, strengthen the inhibition effect of GABA, decrease the excitotoxicity of glutamic acid, and consequently attenuate the secondary degeneration.